The present disclosure relates to implantable drug delivery and electrical stimulation systems and methods, and more particularly relates to utilizing one or more such implantable devices for treating coronary artery disease and angina.
Coronary artery disease (CAD) caused over 450,000 deaths in 1997 and is a major leading cause of death in America today. Approximately 12 million Americans have a history of myocardial infarction (MI, i.e., heart attack), angina pectoris, or both. The American Heart Association estimates the annual cost of treating CAD to be about $118.2 billion.
The major symptoms of CAD include angina pectoris and MI. Angina may be described as a discomfort, a heaviness, or a pressure in the chest. It may also be described as an aching, burning, or squeezing pain. Angina is usually felt in the chest, but may also be felt in the left shoulder, arms, neck, throat, jaw, or back. Other symptoms that can occur with CAD include dyspnea (shortness of breath), palpitations (irregular heart beats or skipped beats), tachycardia (faster heart rate), weakness or dizziness, nausea, and perspiration.
Coronary artery disease is caused by atherosclerotic narrowing of the coronary arteries. As most people age, fatty deposits form and thicken on arterial walls, causing injury to the walls of these blood vessels. Other substances floating through the bloodstream, including inflammatory cells, proteins, and calcium, stick to these injury sites. The fat and other substances combine and lead to the development of atheromas, which are complex atherosclerotic plaques consisting of lipids, fibrous tissue, collagen, calcium, cellular debris, and capillaries. As the plaque thickens, it narrows the artery. As the lumen narrows, resistance to flow increases and myocardial blood flow is compromised.
Many of these plaque deposits are hard on the outside and soft on the inside. The hard surface can crack or tear, exposing the soft, fatty inside. When this happens, platelets are activated, and a thrombus (blood clot) forms around the plaque, further narrowing the artery.
In addition to this thrombus formation initiated by platelet aggregation, the myocardium may also be injured due to CAD by one of the following mechanisms: progressive luminal narrowing by plaque enlargement, hemorrhage into the atheromatous plaque, embolization of a thrombus or plaque fragment, and coronary artery spasm.
A thrombus may completely block a coronary artery, causing a condition called acute coronary syndrome. This is a name for three types of CAD that are associated with sudden rupture of plaque inside a coronary artery: unstable angina, non-Q wave MI, and Q wave MI. The type of acute coronary syndrome is determined by the length of time blood flow is blocked and the amount of damage that occurs. A small plaque, which may not be detectable by stress testing or cardiac catheterization, can cause an acute coronary syndrome. Prior symptoms may or may not be present.
Oxygen demand that exceeds coronary vessels' capacity can cause localized ischemia. When tissue becomes ischemic, loss of function occurs within minutes. Transient ischemia causes reversible changes at the cellular and tissue level. Lack of oxygen causes a shift from aerobic to anaerobic metabolism, which increases lactic acid production, decreases cellular pH, and increases hydrogen ion concentration. Left ventricular function is impaired, causing incomplete emptying on systole, which in turn decreases cardiac output and increases left ventricular end diastolic pressure. This may lead to increased heart rate and blood pressure (hypertension), prior to the onset of pain. This cardiovascular response is a sympathetic compensation in response to the depression of myocardial function. With pain, there is also an increase in catecholamine release. Ischemic attacks subside within minutes if the imbalance between myocyte (a.k.a., cardiac cells) supply and demand for oxygen is corrected.
As is well known in the art, the electrocardiogram (ECG) signs of impending, evolving, and completed infarction follow a course from peaked T waves to elevated ST segments, to development of Q waves, to development of T wave inversion and resolution of ST segment elevation. The abnormalities to look for are “significant” Q waves, loss of precordial R height, ST elevation in contiguous leads, and T wave peaking or inversion. Any combination of these ECG abnormalities can be present during the evolution of infarction.
Prolonged cardiac ischemia (i.e., more than 30-40 minutes) causes irreversible cellular damage and necrosis, loss of myocardial contraction, and alteration of action potential conduction. Myocardial infarction (Ml) is ischemic death of myocardial tissue associated with obstruction of a coronary vessel. This myocardial area of infarction becomes necrotic due to an absolute lack of blood flow. The necrotic cells are inactive electrically and their cell membranes rupture, releasing their cellular contents into the interstitial spaces. Potassium release by these cells interferes with the electrical activity of surrounding cells and leads to arrhythmias (usually premature ventricular contractions (PVCs)).
Most episodes of myocardial ischemia leading to an acute MI occur in the early morning hours. This may be related to diurnal rhythms of catecholamines and cortisol levels as well as enhanced platelet aggregation.
A narrowed vessel may develop collateral circulation. That is, small capillary-like branches of the artery may form over time in response to narrowed coronary arteries. The collaterals “bypass” the area of narrowing and help to restore blood flow. However, during times of increased exertion, the collaterals may not be able to supply enough oxygen-rich blood to the heart muscle.
Existing treatments for CAD suffer from a variety of disadvantages. Currently used medications tend to improve blood circulation (i.e., oxygen supply) to the heart only acutely, if at all. (Vasodilators can improve blood supply a bit.) Existing surgical procedures are invasive, have high morbidity, and/or are often only temporarily beneficial. What is needed are systems and methods to effectively and efficiently deliver drugs, possibly in combination with electrical stimulation, to appropriate treatment sites to treat CAD and relieve patients of its symptoms.